Nirmatrelvir/ritonavir Use With Tacrolimus in Lung Transplant Recipients: A Single-center Case Series.

BACKGROUND: Limited data and guidelines exist for using nirmatrelvir/ritonavir in solid organ transplant recipients stabilized on tacrolimus for the treatment of mild-to-moderate coronavirus disease. Concern exists regarding the impact of utilizing a 5-d course of nirmatrelvir/ritonavir with calcineurin inhibitors because of significant drug-drug interactions between ritonavir, a potent cytochrome P450 3A inhibitor, and other cytochrome P450 3A substrates, such as tacrolimus. METHODS: We report the successful use of nirmatrelvir/ritonavir in 12 outpatient lung transplant recipients with confirmed severe acute respiratory syndrome coronavirus 2 infection stabilized on tacrolimus immunosuppression. All patients stopped tacrolimus and started nirmatrelvir/ritonavir 10 to 14 h after the last dose of tacrolimus. Tacrolimus was withheld and then reinitiated at a modified dose 48 h following the completion of nirmatrelvir/ritonavir therapy. Tacrolimus trough levels were checked during nirmatrelvir/ritonavir therapy and tacrolimus reinitiation. RESULTS: Ten (10/12) patients were able to resume their original tacrolimus dose within 4 d of completing nirmatrelvir/ritonavir therapy and maintain therapeutic levels of tacrolimus. No patients experienced tacrolimus toxicity or acute rejection during the 30-d postcompletion of nirmatrelvir/ritonavir therapy. CONCLUSIONS: In this cohort of lung transplant recipients on tacrolimus, we demonstrated that nirmatrelvir/ritonavir can be safely used with close monitoring of tacrolimus levels and appropriate dose adjustments of tacrolimus. Further confirmatory studies are needed to determine the appropriate use of therapeutic drug monitoring and tacrolimus dose following completion of nirmatrelvir/ritonavir in the solid organ transplant population.

Pandemic grief risk factors and prolonged grief disorder in bereaved young adults during COVID-19.

OBJECTIVES: This study evaluated whether COVID-19-specific risk factors (e.g., feeling guilty for not being present with the deceased at the time of the loss and feeling emotionally distant from the deceased prior to the loss) were associated with prolonged grief disorder (PGD) symptomatology or diagnosis among young adults bereaved due to any cause (e.g., illness and violent loss). METHODS: We surveyed 196 young adults who had a family member/close friend die during the COVID-19 pandemic. Participants completed the PGD-12 Questionnaire and the 10-item Pandemic Grief Risk Factors (PGRF) Questionnaire. RESULTS: More time spent with the deceased before the loss and greater endorsement of pandemic grief risk factors were associated with increased PGD symptoms and a greater likelihood of meeting the diagnostic criteria for PGD. SIGNIFICANCE OF RESULTS: The COVID-19 pandemic created unique risk factors that affected the grieving process for bereaved individuals, regardless of whether the death was related to COVID-19 infection. These findings add to a growing body of literature examining grief and loss within the unique context of the COVID-19 pandemic and suggest that there may be detrimental long-term psychological outcomes for these bereaved individuals, regardless of the cause of death. Routine screening for these unique risk factors in medical and psychological clinics is warranted to help identify those individuals who could benefit from early intervention. Also, it will be important to understand and possibly modify evidence-based interventions and prevention programs to directly address the identified unique PGRF.

Public stigma toward prolonged grief and COVID-19 bereavement: A vignette-based experiment.

We investigated the effects of cause of death and the presence of prolonged grief disorder (PGD) on eliciting public stigma toward the bereaved. Participants (N = 328, 76% female; Mage = 27.55 years) were randomly assigned to read one of four vignettes describing a bereaved man. Each vignette differed by his PGD status (PGD diagnosis or no PGD diagnosis) and his wife's cause of death (COVID-19 or brain hemorrhage). Participants completed public stigma measures assessing negative attributions, desired social distance, and emotional reactions. Bereavement with PGD (versus without PGD) elicited large and significantly stronger responses across all stigma measures. Both causes of death elicited public stigma. There was no interaction between cause of death and PGD on stigma. With increased PGD rates expected during the pandemic, the potential for public stigma and reduced social support for people bereaved via traumatic deaths and people with PGD requires mitigation.

Quality of Life Outcomes and Associated Symptoms Reported by Lung Transplant Recipients Amidst COVID-19 Pandemic: Applying a Novel Assessment Tool.

BACKGROUND: There are 2 main aims of lung transplantation for people with end-stage lung disease: (1) to extend life and (2) to improve its quality. Much consideration is given to how to support the longevity and functioning of the allograft, though less robust studies have been done on the quality of the recipients' lives. With an interest in providing compassionate and holistic patient-centered care, it is vital that the treatment providers accurately understand their patients' lived experience. This study aimed to describe the health-related quality of life experiences of lung transplant recipients. An interest was held for where patients may struggle, thus informing where support might be needed to achieve the best possible outcomes. METHODS: This single-center study used a validated Lung Transplant Quality of Life questionnaire, which was sent in autumn of 2020 to all of the lung transplant recipients (n = 581) under the care of Columbia University Irving Medical Center (New York, NY). RESULTS: "Anxiety/Depression" had the highest concentration of struggle responses, followed closely by "Pulmonary Symptoms" and "Neuromuscular Symptoms." "Neuromuscular Problems" and "Sexual Problems" had the highest percentage of struggle responses. As the struggles increased, the overall quality of life rating dropped proportionately. There was no correlation between the overall quality of life and graft dysfunction, age, or time out from transplant date. All of the domains held an average rating of "Satisfactory," except "Treatment Burden," which was rated as "Favorable." Those ratings dropped for the cohort of patients who died during the study period. CONCLUSIONS: With the goal of providing comprehensive care at the forefront of transplant priorities, we found the newly developed questionnaire invaluable in targeting areas for quality improvements, mostly notably respecting recipient mental health.

Lung Transplantation for Patients With COVID-19.

The COVID-19 pandemic has caused acute lung injury in millions of individuals worldwide. Some patients develop COVID-related acute respiratory distress syndrome (CARDS) and cannot be liberated from mechanical ventilation. Others may develop post-COVID fibrosis, resulting in substantial disability and need for long-term supplemental oxygen. In both of these situations, treatment teams often inquire about the possibility of lung transplantation. In fact, lung transplantation has been successfully employed for both CARDS and post-COVID fibrosis in a limited number of patients worldwide. Lung transplantation after COVID infection presents a number of unique challenges that transplant programs must consider. In those with severe CARDS, the inability to conduct proper psychosocial evaluation and pretransplantation education, marked deconditioning from critical illness, and infectious concerns regarding viral reactivation are major hurdles. In those with post-COVID fibrosis, our limited knowledge about the natural history of recovery after COVID-19 infection is problematic. Increased knowledge of the likelihood and degree of recovery after COVID-19 acute lung injury is essential for appropriate decision-making with regard to transplantation. Transplant physicians must weigh the risks and benefits of lung transplantation differently in a post-COVID fibrosis patient who is likely to remain stable or gradually improve in comparison with a patient with a known progressive fibrosing interstitial lung disease (fILD). Clearly lung transplantation can be a life-saving therapeutic option for some patients with severe lung injury from COVID-19 infection. In this review, we discuss how lung transplant providers from a number of experienced centers approach lung transplantation for CARDS or post-COVID fibrosis.

Novel suction-based in vivo cutaneous DNA transfection platform.

This work reports a suction-based cutaneous delivery method for in vivo DNA transfection. Following intradermal Mantoux injection of plasmid DNA in a rat model, a moderate negative pressure is applied to the injection site, a technique similar to Chinese báguàn and Middle Eastern hijama cupping therapies. Strong GFP expression was demonstrated with pEGFP-N1 plasmids where fluorescence was observed as early as 1 hour after dosing. Modeling indicates a strong correlation between focal strain/stress and expression patterns. The absence of visible and/or histological tissue injury contrasts with current in vivo transfection systems such as electroporation. Specific utility was demonstrated with a synthetic SARS-CoV-2 DNA vaccine, which generated host humoral immune response in rats with notable antibody production. This method enables an easy-to-use, cost-effective, and highly scalable platform for both laboratorial transfection needs and clinical applications for nucleic acid­based therapeutics and vaccines.

Preloss grief in family members of COVID-19 patients: Recommendations for clinicians and researchers.

Researchers have long examined grief-related reactions to the diagnosis of a loved one with a terminal illness, including preloss grief (PLG), which is the experience of grief symptoms prior to the loss of a loved one. Families face novel challenges when loved ones with COVID-19 become critically ill-most notably mandated physical separation-and may experience a wide range of PLG responses. This commentary examines the existing literature related to PLG as a means for understanding the psychological impact of COVID-19 deaths, identifies factors professionals can assess for and address when working with a family member of COVID-19 patients, and identifies areas for future research related to COVID-19 and PLG. (PsycInfo Database Record (c) 2020 APA, all rights reserved).